Currently ductal carcinoma in situ (DCIS) accounts for 20-30% of newly diagnosed breast cancers in screened populations. Because of the inability to stratify the DCIS populations at high risk for recurrence and disease progression, many women are currently over-treated and approximately 10-15% patients have disease recurrence despite surgical and adjuvant interventions. Preliminary and published data indicate that a large fraction of DCIS lesions exhibits alterations in the ErbB2 and RB-pathways. However there are no studies investigating effects of both pathways abnormalities in the same DCIS lesion. In this application we using functional studies, will: 1. Define role of RB pathway in progression of ErbB2 overexpressing DCIS and 2. Determine how RB and ErbB2 status impacts response to radiation therapy.